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Understanding prion strains and species barriers and devising novel diagnostic approaches

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Title Understanding prion strains and species barriers and devising novel diagnostic approaches
Period 01 / 2007 - unknown
Status Current
Research number OND1318793
Data Supplier Projectleider

Abstract

The existence of stable strains of prions, differing in incubation times, clinical features, and neuro-anatomical PrPSc deposition, is disquieting. The structural and biological features, which encode strains and determine their disease phenotype, are obscure. Some strains, including BSE, easily traverse species barriers causing serious concerns in the EU. Promiscuous strains present a public health threat if they propagate through the food chain, while remaining either undetected or misidentified.These dangers are illustrated by the atypical cases of scrapie, which have appeared throughout the EU, including in sheep hitherto considered genetically resistant, and by the identification of BSE in a goat in France. As yet there are no diagnostic procedures to identify TSE strains, except in some rare cases. We propose studying fundamental and applied aspects of prions strains and their relationship to the species barrier, and to use the knowledge generated to initiate diagnostic methodologies to detect strains and predict their epidemiological behaviour. We have assembled a powerful consortium of partners with proven experimental and industrial achievements.We will(i) systematically examine the properties of field strains and their species barriers when propagated(ii) examine strain-dependent biochemical and biophysical properties of PrPSc(iii) apply novel cryoelectron tomographical techniques to determine the 3-D structure (at 4 nm resolution) of PrPSc in various strains in neuronal (stem) cells(iv) study strain-specific features of prion infection in cultured cells, including their uptake receptors,(v) characterize strain dependent cytopathogenic mechanisms in infected cells.We will prepare novel diagnostic and research reagents such asa) possibly strain specific, PrP monoclonal antibodies,b) a goat PrP transgenic mouse, andc) novel ovine, caprine and bovine neuronal stem cells susceptible to prion infection.

Related organisations

Related people

Researcher S. Godsave (PhD)
Researcher B. Krenn (PhD)
Researcher P. Kujala (PhD)
Researcher P. Res (PhD)
Researcher N. van der Wel (PhD)
Project leader Prof.dr. P.J. Peters

Classification

A22000 Animal husbandry
A71000 Nutrition
D22100 Microbiology
D23110 Infections, parasitology

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